Study of Pembrolizumab With or Without Defactinib Followi... | NCT03727880

ID	Type	Description	Link
STUDY00001506	Other Identifier	UTHSCSA IRB

Status Module

Name	Class
Merck Sharp & Dohme LLC	INDUSTRY
Verastem, Inc.	INDUSTRY

Description Module

Arms/Interventions Module

Label	Type	Description	Intervention Names
Arm A - Pembrolizumab and Defactinib	Experimental		Drug: Pembrolizumab Drug: Defactinib
Arm B - Pembrolizumab	Experimental		Drug: Pembrolizumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Drug	Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Pathologic Complete Response (pCR) Rate	Percent of subjects with a pathologic complete response (pCR) per the tumor regression grade scores established by the College of American Pathologist: Grade 0= complete response (no viable cancer cells), Grade 1= near complete response (single cells or rare small groups of cancer cells), Grade 2= partial response (residual tumor with evidence of regression), or Grade 3= no response (extensive residual tumor with no evidence of regression).	4 years

Measure	Description	Time Frame
Overall Survival (OS)	Number of months until death	4 years
Disease Free Survival (DFS)	Number of months until disease recurrence

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age ≥18 years.
Has pancreatic ductal adenocarcinoma
Has resectable disease at the time of diagnosis
Has not received any systemic therapy for pancreatic ductal adenocarcinoma
Has stage ≤ IIb disease at time of diagnosis and enrollment
Elevated tumor marker, CA (carbohydrate antigen) 19-9 >200
ECOG performance status 0 or 1
Patient must have adequate organ function defined by the study-specified laboratory tests.
Must use acceptable form of birth control while on study.
Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

Patients who have received any prior chemotherapy, radiotherapy or investigational agents for pancreatic cancer.

Patients who have received prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
Has received prior therapy with FAK inhibitor.
Woman who are pregnant or breastfeeding.
Have received a live vaccine or live-attenuated vaccine within 30 days prior to study drug.
Is currently or has participated in another investigational study within 4 weeks prior to receiving study drug.
History or current use of immunosuppressive medications within 7 days prior to study medications.
Has a known additional malignancy that is progressing or has required active treatment within the past 2 years or that is expected to require active treatment within two years.
Has active autoimmune disease that has required systemic treatment in the past 2 years.
Has a history of (non-infectious) pneumonitis/interstitial lung disease or current pneumonitis.
Has an active infection requiring systemic therapy.
Infection with HIV or hepatitis B or C.
Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Known allergy or hypersensitivity to the study drugs.
Received any growth factors including, but not limited to, granulocyte-colony stimulating factor (G-CSF), GM-CSF, erythropoietin, within 14 days of study drug administration.
Has history of any organ transplant, including corneal transplants.

Name	Affiliation	Role
Lei Zheng, MD	The University of Texas Health Science Center San Antonio	Principal Investigator
Arsen Osipov, MD	Cedar Sinai	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Samuel Oschin Cancer Center at Cedars-Sinai		Los Angeles	California	90048	United States
Sidney Kimmel Comprehensive Cancer Center

PubMed Identifier	Type	Citation	Retractions
37598000	Derived	Fard D, Giraudo E, Tamagnone L. Mind the (guidance) signals! Translational relevance of semaphorins, plexins, and neuropilins in pancreatic cancer. Trends Mol Med. 2023 Oct;29(10):817-829. doi: 10.1016/j.molmed.2023.07.009. Epub 2023 Aug 17.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm A - Pembrolizumab and Defactinib	Pembrolizumab: Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart. Defactinib: Following 2 cycles of standard of care neoadjuvant chemotherapy, subjects will receive 400 mg defactinib twice a day up until 2 days preceding their surgery (approximately 6 weeks) during the immunotherapy cycles with pembrolizumab. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 400mg defactinib twice a day for 24 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Aug 5, 2024

Arm/Group Information

ID	Title	Description
BG000	Arm A - Pembrolizumab and Defactinib	Pembrolizumab: Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart. Defactinib: Following 2 cycles of standard of care neoadjuvant chemotherapy, subjects will receive 400 mg defactinib twice a day up until 2 days preceding their surgery (approximately 6 weeks) during the immunotherapy cycles with pembrolizumab. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 400mg defactinib twice a day for 24 weeks.
BG001	Arm B - Pembrolizumab	Pembrolizumab: Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00013 BG00110 BG00223

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00071.54± 11.39 BG00173.5± 6.62 BG00272.4± 9.01

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0006 BG0013 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00013 BG00110 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Pathologic Complete Response (pCR) Rate

Percent of subjects with a pathologic complete response (pCR) per the tumor regression grade scores established by the College of American Pathologist: Grade 0= complete response (no viable cancer cells), Grade 1= near complete response (single cells or rare small groups of cancer cells), Grade 2= partial response (residual tumor with evidence of regression), or Grade 3= no response (extensive residual tumor with no evidence of regression).

Participants that reached pCR

Posted

Number

Percentage of participants

4 years

ID	Title	Description
OG000	Arm A - Pembrolizumab and Defactinib	Pembrolizumab: Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart. Defactinib: Following 2 cycles of standard of care neoadjuvant chemotherapy, subjects will receive 400 mg defactinib twice a day up until 2 days preceding their surgery (approximately 6 weeks) during the immunotherapy cycles with pembrolizumab. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 400mg defactinib twice a day for 24 weeks.
OG001	Arm B - Pembrolizumab	Pembrolizumab: Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart.

Units	Counts
Participants	OG00010 OG0018

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010

Secondary

Overall Survival (OS)

Number of months until death

Participants evaluable were those that were randomized to intervention and completed the study

Posted

Mean

Standard Deviation

months

4 years

ID	Title	Description
OG000	Arm A - Pembrolizumab and Defactinib	Pembrolizumab: Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart. Defactinib: Following 2 cycles of standard of care neoadjuvant chemotherapy, subjects will receive 400 mg defactinib twice a day up until 2 days preceding their surgery (approximately 6 weeks) during the immunotherapy cycles with pembrolizumab. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 400mg defactinib twice a day for 24 weeks.
OG001	Arm B - Pembrolizumab	Pembrolizumab: Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart.

Secondary

Disease Free Survival (DFS)

Number of months until disease recurrence

For Arm A overall study was completed by 13 pt, DFS evalauted for 11. The remaining 2 participants were not evaluable for DFS because surgery was not performed and therefore they never achieved a disease-free baseline For Arm B overall study was completed by 10 pt, DFS evalauted for 8. The 2 participants whose surgeries were attempted but aborted were not evaluable for DFS because they never achieved a disease-free baseline."

Posted

Mean

Standard Deviation

months

4 years

ID	Title	Description
OG000	Arm A - Pembrolizumab and Defactinib	Pembrolizumab: Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart. Defactinib: Following 2 cycles of standard of care neoadjuvant chemotherapy, subjects will receive 400 mg defactinib twice a day up until 2 days preceding their surgery (approximately 6 weeks) during the immunotherapy cycles with pembrolizumab. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 400mg defactinib twice a day for 24 weeks.
OG001	Arm B - Pembrolizumab	Pembrolizumab: Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart.

Secondary

Number of Participants Experiencing Study Drug-related Toxicities

Number of participants experiencing drug-related adverse events as defined by CTCAE v5.0

Includes all participants that both completed and did not complete the study

Posted

Number

participants

4 years

ID	Title	Description
OG000	Arm A - Pembrolizumab and Defactinib	Pembrolizumab: Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart. Defactinib: Following 2 cycles of standard of care neoadjuvant chemotherapy, subjects will receive 400 mg defactinib twice a day up until 2 days preceding their surgery (approximately 6 weeks) during the immunotherapy cycles with pembrolizumab. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 400mg defactinib twice a day for 24 weeks.
OG001	Arm B - Pembrolizumab	Pembrolizumab: Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A - Pembrolizumab and Defactinib	Pembrolizumab: Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart. Defactinib: Following 2 cycles of standard of care neoadjuvant chemotherapy, subjects will receive 400 mg defactinib twice a day up until 2 days preceding their surgery (approximately 6 weeks) during the immunotherapy cycles with pembrolizumab. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 400mg defactinib twice a day for 24 weeks.	10	14	2	14	4	14
EG001	Arm B - Pembrolizumab	Pembrolizumab: Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart.	6	14	3	14	3	14

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Non-pancreatic cancer	General disorders		Systematic Assessment		EG0002 events2 affected14 at risk EG0013 events3 affected14 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Colitis	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected14 at risk EG0018 events1 affected14 at risk
Increased bilirubin	Blood and lymphatic system disorders	Systematic Assessment	EG0009 events3 affected14 at risk EG0010 events0 affected14 at risk
Elevated aspartate aminotransferase (AST)	Hepatobiliary disorders	Systematic Assessment	EG0007 events1 affected14 at risk EG0010 events0 affected14 at risk
Elevated Alanine transaminase (ALT)	Hepatobiliary disorders	Systematic Assessment	EG0008 events1 affected14 at risk EG0010 events0 affected14 at risk
Acnieform rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected14 at risk
Myasthenia gravis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected14 at risk EG0013 events1 affected14 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected14 at risk

ID	Term
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004701	Endocrine Gland Neoplasms
D004066	Digestive System Diseases
D010182	Pancreatic Diseases
D004700	Endocrine System Diseases